Antibacterial composition and method

ABSTRACT

An antimicrobial composition consisting of ampicillin and L-3(3,4-dihydroxyphenyl)alanine or 3,4-dihydroxyphenylacetic acid is more efficacious than ampicillin alone in the treatment of pyelonephritis.

United States Patent 91 Burrous et al.

[ 1 Jan. 30, 1973 [54] ANTIBACTERIAL COMPOSITION AND METHOD [75]Inventors: Stanley E. Burrous; William W.

Eudy; Arthur J. Siedler, all of Norwich, NY.

[73] Assignee: Morton-Norwich Products, Inc.

[22] Filed: Jan. 18, 1971 [21] App]. No.: 107,518

[52] US. Cl. ..424/27l, 424/317, 424/319 [51] Int. Cl. ..A6lk 21/00 [58]Field of Search ..424/27l, 317, 319

[5 6] References Cited OTHER PUBLICATIONS The Merck Index, 8th Edition,1968, pages 75 and 397.

Primary Exqminer-Jerome D. Goldberg Att0rneyBradford S. Allen [57]ABSTRACT I 2 Claims, No Drawings ANTIBACTERIAL COMPOSITION AND METHODThis invention relates to antimicrobial therapy. More particularly it isconcerned with antimicrobial therapy through a composition consisting ofampicillin and L-3- (3,4-dihydroxyphenyl)alanine (levodopa) or 3,4-dihydroxyphenylacetic acid (dopac).

Ampicillin is a valuable anti-infective agent. However, in keeping withmost therapeutic agents, side effects are oftentimes encountered. Oneside effect associated with ampicillin therapy is diarrhea which isnoted in both animals, such as the rat, and humans. In the latter, thisside effect sometimes approaches such severity that valuable therapymust be withdrawn.

We have discovered that the dosage of ampicillin necessary to achievetherapeutic results can be markedly reduced through the concomitantadministration of ampicillin and levodopa or dopac. Such potentiationaffords a continuance of therapy in the side effect susceptible host andthus greater latitude of therapy with lesser risk of inducing unwantedside effects.

In accordance with this invention pyelonephritis is produced in onekidney of the rat by inoculation of that organ with a saline suspensionof a culture of Escherichia coli, the other serving as control. Afterinfection of the kidney had been established, the organ was removed byexcision and examined for viable bacteria either by brain-heart agarplate count or by an Aminco automatic diluter. This method of infectingrat kidneys and determining infectivity is more fully described inApplied Microbiology, Sept. 1969, p. 448-451.

Ampicillin administered by gavage, perorally, in a 1 percent sodiumcarboxymethylcellulose suspension at a dose of mg/kg b.i.d. to soinfected rats achieved only marginal therapeutic benefit. Neitherlevodopa nor dopac similarly administered in doses varying from 40-100mg/kg evinced any therapeutic benefit. When ampicillin at the borderlineeffective dose of 20 mg/kg and from 40-100 mg/kg of levodopa or dopacwere similarly administered together a surprising reduction of viablebacteria was effected. A lower dose of ampicillin of 7 mg/kg inconjunction with a 100 mg/kg amount of levodopa also produced resultsnot attributable to either alone. The table herebelow depicts theresults achieved:

Titers of Viable Bacteria in Rat Unilateral Escherichia coliPyelonephritis Oral, b.i.d., Therapy commencing 3 days after infectionand continuing for 14 days.

Log of geometric mean of viable No. Dose, bacterial titers of Exp. ofrats Compound mg/kg 5 or 10 kidneys 1 10 control 4.7 10 ampicillin 204.4 10 levodopa 40 4.3 10 levodo a 40 ampici lin 20 2.8 2 5 Control 4.35 ampicillin 20 3.3 5 levodo a 100 4.2 5 ampici lin 20 levodopa 100 2.53 10 Control 4.8 10 ampicillin 20 3.9 10 dopac 40 4.8 10 ampicillin 20dopac 40 3.1 4 10 Control 4.8 10 ampicillin 7 3.8 10 levodo a 100 4.0 10ampici lin 7 levodopa 100 3.3

What is claimed is:

l. A potentiated antibacterial composition consisting of ampicillin andL-3-(3,4-dihydroxyphenyl) alanine or 3,4-dihydroxyphenylacetic acid inthe proportion of from 1:2 to 1:5.

2. A method for treating bacterial infections in an animal whichcomprises orally administering to said animal an antibacteriallyeffective amount of the composition as define in claim 1.

1. A potentiated antibacterial composition consisting of ampicillin andL-3-(3,4-dihydroxyphenyl) alanine or 3,4-dihydroxyphenylacetic acid inthe proportion of from 1:2 to 1:5.